0001725160FALSE00017251602025-01-292025-01-29


UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
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FORM 8-K
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CURRENT REPORT

Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of report (Date of earliest event reported): January 29, 2025

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ZENTALIS PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)   
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Delaware 001-39263 82-3607803
(State or other jurisdiction
of incorporation or organization)
 
(Commission
File Number)
 
(I.R.S. Employer
Identification No.)
10275 Science Center Drive, Suite 200
San Diego, California 92121
(Address of principal executive offices) (Zip Code)
(858) 263-4333
(Registrant’s telephone number, include area code)
N/A
(Former name or former address, if changed since last report)  
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
 
☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
 
☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) 
 
☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) 
 
☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) 



Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading Symbol(s)Name of each exchange on which registered
Common Stock, $0.001 par value per shareZNTLThe Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
 
 



Item 7.01 Regulation FD Disclosure.

On January 29, 2025, Zentalis Pharmaceuticals, Inc. (“Zentalis” or the “Company”) issued the press release furnished as Exhibit 99.1 to this Current Report on Form 8-K (this “Current Report”) and incorporated herein by reference. In addition, on January 29, 2025, spokespersons for the Company presented the information in the Corporate Event Presentation furnished as Exhibit 99.2 to this Current Report, and incorporated herein by reference, at the Company’s corporate event on January 29, 2025 (the “Corporate Event”) and plan to present the information in the Corporate Event Presentation in meetings with investors and analysts. The Corporate Event was presented via live webcast, and an archived recording is available under the “Events & Presentations” tab on the “Investors & Media” section of the Company’s website.

The information contained in Item 7.01 of this Current Report (including Exhibits 99.1 and 99.2 attached hereto) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, except as expressly provided by specific reference in such a filing.

Item 8.01 Other Events.

Azenosertib Development Plan for PROC Monotherapy

On January 29, 2025, the Company announced that it would, as an initial matter, focus its development efforts for its WEE1 inhibitor product candidate, azenosertib, on patients with platinum-resistant ovarian cancer (“PROC”) whose tumors are Cyclin E1-positive as determined utilizing an immunohistochemistry (“IHC”) assay and Zentalis’ proprietary IHC cutoff.

The Company has aligned with the U.S. Food and Drug Administration (“FDA”) on the design of its DENALI Part 2 study in patients with Cyclin E1-positive PROC, which allows for seamless enrollment across Parts 2a and 2b: Part 2a is designed to confirm the primary dose-of-interest, 400mg QD 5:2 (intermittent daily dosing on a five days on, two days off schedule), with a target enrollment of approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2. Part 2b is designed to enroll approximately 70 patients at a single dose, the selection of which will be informed by the Part 2a results, with the final Part 2b dose selection and endpoints subject to FDA feedback. The Company plans to initiate enrollment of DENALI Part 2 in the first half of 2025 and to disclose topline data from DENALI Part 2 by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review.

Azenosertib Clinical Results

Also on January 29, 2025, the Company announced certain clinical results for azenosertib, including the following:

•ZN-c3-001: ZN-c3-001 is a Phase 1, dose-escalation study that evaluated azenosertib monotherapy in solid tumors across continuous and intermittent dosing schedules. ZN-c3-001 is fully enrolled (n=274). Greater anti-tumor activity was seen with intermittent dose schedules and in Cyclin E1-positive patients.

There were 23 patients with Cyclin E1-positive PROC who were dosed at intermittent schedules at total daily doses of ≥300mg. In these patients as of the December 2, 2024 data cutoff, an objective response rate (“ORR”) of 34.8% (8/23; 95% CI: 16.4-57.3) and a median duration of response (“mDOR”) of 5.2 months (95% CI: 2.8, 6.9) were observed.

There were 11 patients with Cyclin E1-positive uterine serous carcinoma who were dosed at intermittent schedules at total daily doses of ≥300mg. In these patients as of the December 2, 2024 data cutoff, an ORR of 36.4% (4/11; 95% CI: 10.9-69.2) and an mDOR of 5.5 months (95% CI: 5.4, not estimable) were observed. The upper end of the mDOR confidence interval was not estimable due to the small number of patients and events.



There were 4 patients with Cyclin E1-positive other solid tumors who were dosed at intermittent schedules at total daily doses of ≥300mg. In these patients as of the December 2, 2024 data cutoff, there were no responders.

There were 193 patients in ZN-c3-001 at total daily doses of ≥300mg across all tumor types and regardless of biomarker status. In these patients as of the December 2, 2024 data cutoff, azenosertib was shown to be tolerable with no Grade 3+ gastrointestinal treatment-related adverse events (“TRAEs”) observed and low rates of Grade 3+ hematological toxicity, with the majority of hematological toxicity events being Grade 3. In these patients, there was also a low rate of TRAEs leading to discontinuation (n=10, 5.2%). There was one previously disclosed treatment-related Grade 5 event in the study (n=1, 0.5%).

•MAMMOTH (ZN-c3-006): MAMMOTH is a multi-arm study that evaluated azenosertib monotherapy and in combination with niraparib in patients with PARP-inhibitor resistant ovarian cancer.

MAMMOTH is fully enrolled. In the monotherapy arm of the study (n=61), patients who were PARPi refractory were treated with azenosertib at 300 mg QD 5:2 or 400 mg QD 5:2. As of the December 2, 2024 data cutoff, among Cyclin E1-positive patients treated at the primary dose-of-interest, 400 mg QD 5:2 (n=16), an ORR of 31.3% (5/16; 95% CI: 11.0 - 58.7) and an mDOR of 4.2 months (95% CI: 3.0, not estimable) were observed, and among Cyclin E1-positive patients treated at the 300 mg QD 5:2 dose level (n=14), an ORR of 21.4% (3/14; 95% CI: 4.7 – 50.8) and an mDOR of 4.9 months (95% CI: 3.0 – not estimable) were observed. The upper end of the mDOR confidence interval was not estimable due to the small number of patients and events.

As of the December 2, 2024 data cutoff, in the monotherapy arm of the MAMMOTH study at both 300mg QD 5:2 and 400mg QD 5:2 regardless of biomarker status, similar rates of treatment-related serious adverse events (“SAEs”) were observed across dose levels. There was a low rate of treatment-related Grade 3+ hematological toxicity with the majority being Grade 3 events. There was a low rate of TRAEs leading to treatment discontinuation: 16% in the 300 mg arm (n=4) and 5.6% in the 400 mg arm (n=2). There was one previously reported treatment-related Grade 5 event in the study.

In the combination arms of the study, where azenosertib was dosed on a concurrent or alternating schedule with niraparib, although no new safety signals were observed, efficacious exposures of azenosertib were not reached, and the Company is not proceeding further with development of the combination with niraparib.

•DENALI (ZN-c3-005) Part 1b: DENALI Part 1b is a single-arm study that evaluated azenosertib monotherapy at the 400mg QD 5:2 dose in patients with PROC (n=102). Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1-positive per the Company’s proprietary IHC cutoff.

As of the December 2, 2024 data cutoff, in patients with Cyclin E1-positive PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib), an ORR of 34.9% (15/43; 95% CI: 21.0 - 50.9) was observed. In the intent-to-treat patients with Cyclin E1-positive PROC (patients who received at least one dose of azenosertib), the ORR was 31.3% (15/48; 95% CI: 18.7 - 46.3). As of the December 2, 2024 data cutoff, the mDOR for the intent-to-treat population was still maturing and was approximately 5.5 months (95% CI: 2.7 - not estimable).

As of the December 2, 2024 data cutoff, a safety and tolerability profile broadly consistent with ZN-c3-001 and MAMMOTH monotherapy was observed. There were two previously reported treatment-related Grade 5 events in the study (n=2, 2.0%).

•ZN-c3-016: ZN-c3-016 is a Phase 1/2 study that evaluated azenosertib in combination with encorafenib and cetuximab in patients with metastatic BRAF V600E mutant colorectal cancer in collaboration with Pfizer.

The dose-finding phase of the ZN-c3-016 study is fully enrolled (n=44). Of the 44 enrolled, 34 patients were BRAF-inhibitor naïve and 10 had previously been treated with a BRAF-inhibitor. As of the November 25, 2024 data cutoff, 12 of the 34 BRAF-inhibitor ("BRAFi") naïve patients (35%) had a confirmed


response (2 complete responses, 10 partial responses), 7 of the 17 patients treated at azenosertib 300 mg + encorafenib 150 or 75 mg + cetuximab (41%) had a confirmed partial response, and none of the BRAFi-experienced patients had a confirmed response.

As of the November 25, 2024 data cutoff, the most frequent treatment-related Grade 3+ adverse events were asthenia (11.4%) and fatigue (6.8%), dose-limiting toxicities were observed at the dose levels of azenosertib 300mg + encorafenib 150mg and azenosertib 400mg + encorafenib 75mg and included dose-limiting fatigue, atrial fibrillation, recurring elevated bilirubin (all Grade 3), and Grade 4 neutropenia, and there was one treatment-related Grade 5 event that was previously disclosed. The maximum tolerated dose was determined to be azenosertib 300mg + encorafenib 75mg.

While the results in BRAF inhibitor naïve patients were encouraging, the Company decided not to advance into the dose expansion phase of the study due to resource prioritization and an evolving treatment landscape.

Cautionary Note Regarding Forward-Looking Statements

This Current Report contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended. All statements in this Current Report that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the Company’s planned development strategy for azenosertib; the Company's plan to initiate enrollment of DENALI Part 2 and the timing thereof; the planned design of DENALI Part 2, including target enrollment numbers; the potential for DENALI Part 2, if successful, to support an accelerated approval for azenosertib; and the Company’s plans to present data from its clinical trials in the future, including the timing of topline data from DENALI Part 2. The terms “designed,” “plan,” “potential,” “will,” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause the Company’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the Company’s limited operating history, which may make it difficult to evaluate the Company’s current business and predict the Company’s future success and viability; the Company has and expects to continue to incur significant losses; the Company’s need for additional funding, which may not be available; the Company’s plans, including the costs thereof, of development of companion diagnostics; the Company’s substantial dependence on the success of our lead product candidate, azenosertib; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; the Company’s product candidates may cause serious adverse side effects; inability to maintain collaborations, or the failure of these collaborations; the Company’s reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; the Company’s ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in the Company’s most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the SEC and the Company’s other filings with the SEC. These forward-looking statements (except as otherwise noted) speak only as of the date of this Current Report, and the Company does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this Current Report.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
The following Exhibits 99.1 and 99.2 relating to Item 7.01 shall be deemed to be furnished, and not filed:


Exhibit No.
 Description
 
104Cover Page Interactive Data File (embedded within the inline XBRL document)



SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
 
 ZENTALIS PHARMACEUTICALS, INC.
Date: January 29, 2025 By: /s/ Julie Eastland
  Julie Eastland
  President and Chief Executive Officer

image_0.jpg
Exhibit 99.1


Zentalis Pharmaceuticals Shares Updated Clinical Data Demonstrating Meaningful Azenosertib Activity in Cyclin E1+, Platinum-Resistant Ovarian Cancer

Results from DENALI Part 1b show an Objective Response Rate (ORR) of ~35% in response-evaluable, heavily-pretreated patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC)

Across monotherapy cohorts in key clinical studies, well-characterized safety and tolerability profile shows no new safety signals

Company aligned with FDA on seamless study design for DENALI Part 2 in patients with Cyclin E1+ PROC; study expected to begin 1H 2025

Topline data from registration-intent DENALI Part 2 anticipated by year end 2026

Management to host conference call today at 8:00 am ET

SAN DIEGO — January 29, 2025 — Zentalis® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, today presented updated azenosertib monotherapy clinical data from its ZN-c3-001, MAMMOTH and DENALI studies and shared details on future clinical development and potential registration plans for patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC). Results from the combination cohorts of MAMMOTH and from the ZN-c3-016 study in colorectal cancer were also disclosed today.

"We are excited to outline a clear path for Zentalis to bring azenosertib to patients with Cyclin E1+ PROC,” said Ingmar Bruns, M.D., Chief Medical Officer. “In a patient population with a clear unmet medical need, the monotherapy data showed a meaningful and consistent improvement in responses as compared to historical data from current monotherapy chemo standard of care, across multiple studies, in heavily-pretreated patients at the 400mg QD 5:2 intermittent dose. The results demonstrate a median duration of response of approximately 5.5 months that continues to mature with patients remaining on therapy. In addition, with over 350 patients treated at clinically active monotherapy doses (total daily dose ≥ 300mg) across our studies, we have observed a well-characterized safety profile and no new safety signals since our last report. Our data have also confirmed Cyclin E1 overexpression as a predictor of sensitivity to azenosertib monotherapy in PROC, and we intend to pursue further development in this patient population.”

“We are very pleased with the azenosertib results obtained to date and believe we have a clear path to advancing this product candidate to patients,” said Julie Eastland, Chief Executive Officer. “Notably, approximately 50% of patients with PROC are Cyclin E1+, and we believe that the therapeutic and commercial opportunity in this population, which tends to be especially treatment-refractory, is substantial. Looking ahead at continued azenosertib development, we believe that DENALI Part 2, if successful, has the potential to support an accelerated product approval, subject to FDA feedback. Together with the corporate restructuring announced yesterday that extended our cash runway into late


2027, well beyond the anticipated topline data readout from DENALI Part 2, Zentalis is well-positioned to execute on our goal to bring azenosertib to patients as quickly as possible.”

The Company plans to present the following at the corporate event:

DENALI Part 2 Study Design
The Company has aligned with the U.S. Food and Drug Administration (FDA) on the design of its DENALI Part 2 study in patients with Cyclin E1+ PROC, which allows for seamless enrollment across Parts 2a and 2b: Part 2a is designed to confirm the primary dose-of-interest, 400mg QD 5:2 (intermittent daily dosing on a five days on, two days off schedule), with a target enrollment of approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2. Part 2b is designed to enroll approximately 70 patients at a single dose, the selection of which will be informed by the Part 2a results, with the final Part 2b dose selection and endpoints subject to FDA feedback. The Company plans to initiate enrollment of DENALI Part 2 in the first half of 2025 and to disclose topline data from DENALI Part 2 by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review.

Azenosertib Clinical Results
ZN-c3-001
ZN-c3-001 is a Phase 1, dose-escalation study that evaluated azenosertib monotherapy in solid tumors across continuous and intermittent dosing schedules.

ZN-c3-001 is fully enrolled (n=274). As of the December 2, 2024 data cutoff, results from ZN-c3-001 showed encouraging ORR and median duration of response (mDOR) at a total daily dose level ≥300mg in patients with Cyclin E1+ PROC who were dosed at an intermittent schedule (n=23). In these patients, an ORR of 34.8% (8/23; 95% CI: 16.4-57.3) and an mDOR of 5.2 months (95% CI: 2.8, 6.9) were observed. Full efficacy results at a total daily dose level ≥300mg across biomarker status and tumor types will be shared in the presentation.

In the ZN-c3-001 study, as of the December 2, 2024 data cutoff, azenosertib was shown to be tolerable at a total daily dose level ≥300mg (n=193) across all tumor types and regardless of biomarker status, with no Grade 3+ gastrointestinal treatment-related adverse events (TRAEs) observed and low rates of Grade 3+ hematological toxicity, with the majority of hematological toxicity events being Grade 3. There was also a low rate of TRAEs leading to discontinuation (n=10, 5.2%). There was one previously reported treatment-related Grade 5 event in the study (n=1, 0.5%). Additional safety results at clinically active dose levels across tumor types will be shared in the presentation.

MAMMOTH (ZN-c3-006)
MAMMOTH is a multi-arm study that evaluated azenosertib monotherapy and in combination with niraparib in patients with PARP-inhibitor resistant ovarian cancer.

MAMMOTH is fully enrolled. In the monotherapy arm of the study (n=61), patients who were PARPi refractory were treated with azenosertib at the 300mg QD 5:2 or 400mg QD 5:2. As of the December 2, 2024 data cutoff, among Cyclin E1+ patients treated at the primary dose-of-interest, 400mg QD 5:2 (n=16), an ORR of 31.3% (5/16; 95% CI: 11.0 - 58.7) and an mDOR of 4.2 months (95% CI: 3.0 - not


estimable) were observed. The upper end of the mDOR confidence interval was not estimable due to the small number of patients and events. Efficacy results across dose levels and biomarker status will be shared in the presentation.

As of the December 2, 2024 data cutoff, in the monotherapy arm of the MAMMOTH study at both 300mg QD 5:2 and 400mg QD 5:2 regardless of biomarker status, similar rates of treatment-related serious adverse events (SAEs) were observed across dose levels. There was a low rate of treatment-related Grade 3+ hematological toxicity with the majority being Grade 3 events. There was a low rate of TRAEs leading to treatment discontinuation: 5.6% in the 400mg arm (n=2). There was one previously reported treatment-related Grade 5 event in the study (n=1, 1.6%). Additional safety results across dose levels will be shared in the presentation.

In the combination arms of the study, where azenosertib was dosed on a concurrent or alternating schedule with niraparib, although no new safety signals were observed, efficacious exposures of azenosertib were not reached, and the Company is not proceeding further with development of the combination with niraparib.

DENALI (ZN-c3-005) Part 1b
DENALI Part 1b is a single-arm study that evaluated azenosertib monotherapy at the 400mg QD 5:2 dose in patients with PROC (n=102). Tissue collection for biomarker assessment was mandated in the study and upon a retrospective analysis, approximately 50% of the patients were Cyclin E1+ per the Company’s proprietary cutoff.

As of the December 2, 2024 data cutoff, in patients with Cyclin E1+ PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib), an ORR of 34.9% (15/43; 95% CI: 21.0 - 50.9) was observed. In the intent-to-treat patients with Cyclin E1+ PROC (patients who received at least one dose of azenosertib), the ORR was 31.3% (15/48; 95% CI: 18.7 - 46.3). As of the December 2, 2024 data cutoff, the mDOR for the intent-to-treat population was still maturing and was approximately 5.5 months (95% CI: 2.7 - not estimable).

As of the December 2, 2024 data cutoff, a safety and tolerability profile broadly consistent with ZN-c3-001 and MAMMOTH monotherapy was observed. There were two previously reported treatment-related Grade 5 events in the study (n=2, 2.0%). Additional safety results will be shared in the presentation.

ZN-c3-016
ZN-c3-016 is a Phase 1/2 study that evaluated azenosertib in combination with encorafenib and cetuximab in patients with metastatic BRAF V600E mutant colorectal cancer in collaboration with Pfizer.

The dose-finding phase of the ZN-c3-016 study is fully enrolled (n= 44). 34 patients were BRAF-inhibitor naïve and 10 had previously been treated with a BRAF-inhibitor. Topline results as of the November 25, 2024 data cutoff can be found in the appendix of the presentation. While the results in BRAF inhibitor naïve patients were encouraging, the Company decided not to advance into the dose expansion phase of the study due to resource prioritization and an evolving treatment landscape.



Corporate Event Details
On January 29, 2025, at 8:00am ET Zentalis will host a virtual corporate event to present data from its studies of azenosertib and provide a regulatory update. Access to a live webcast of this event, as well as an archived recording, will be available under the “Events & Presentations” tab on the Investors & Media section of the Company’s website. Analysts who wish to join the teleconference and participate in Q&A should register here.

About Azenosertib
Azenosertib is a novel, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated as a monotherapy and combination clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

About Zentalis Pharmaceuticals
Zentalis® Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing azenosertib (ZN-c3), a potentially first-in-class and best-in-class WEE1 inhibitor for patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC). Azenosertib is being evaluated as a monotherapy and in combination across multiple tumor types in clinical trials and has broad franchise potential. In clinical trials, azenosertib has been well tolerated and has demonstrated anti-tumor activity as a single agent across multiple tumor types. The Company is also leveraging its extensive experience and capabilities to translate its science to advance research on additional areas of opportunity for azenosertib outside PROC. Zentalis has operations in San Diego.

For more information, please visit www.zentalis.com. Follow Zentalis on X/Twitter at @ZentalisP and on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the potential of azenosertib; our plans to hold a corporate event and present clinical data and provide a development and regulatory update, including the timing and content thereof; our anticipated milestones and the timing thereof, including the anticipated timing of initiation of clinical trials and timing of clinical data disclosures; the potential to advance research on additional areas of opportunity for azenosertib outside PROC; our anticipated cash runway; the potential for azenosertib to be first-in-class and best-in-class; the broad franchise potential of azenosertib; the potential of azenosertib to address an unmet need in patients with Cyclin E1+ PROC and our plans to pursue further development in this patient population; our belief that we have a clear path to advance azenosertib to patients; the planned design of our clinical trials, including target enrollment numbers; the potential for Cyclin E1 to serve as a predictor for sensitivity to azenosertib; the therapeutic and commercial opportunity for azenosertib; the potential for DENALI Part 2 to support an accelerated approval for azenosertib; our positioning to execute; and our planned clinical development strategy and regulatory strategy for azenosertib and the timing thereof, including plans for registration-intent studies


and the potential for accelerated approval. The terms “ahead,” “anticipated,” “believe,” “design,” “excited,” “expect,” “further,” “future,” “goal,” “intent,” “opportunity,” “path,” “plan,” “potential,” "promising,” “target,” and “will” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our plans, including the costs thereof, of development of companion diagnostics; our substantial dependence on the success of our lead product candidate, azenosertib; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Statements such as “compared to historical data” indicate that no head-to-head clinical trial has been conducted evaluating azenosertib against the indicated therapies. Notable differences exist between the Company’s trial designs, conditions under study and subject characteristics as compared to the evaluated third party results and caution should be exercised when comparing data across these studies.

ZENTALIS® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release.

Contact:
Elizabeth Pingpank Hickin
ehickin@zentalis.com
860-463-0469


Corporate Event January 29, 2025 Nasdaq: ZNTL Exhibit 99.2

 
2 Zentalis Pharmaceuticals, Inc. (“we,” “us,” “our,” “Zentalis” or the “Company”) cautions that this presentation (including oral commentary that accompanies this presentation) contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential for azenosertib (ZN-c3) to be first-in-class and best-in-class; the potential regulatory pathway for azenosertib, including the potential for azenosertib to utilize an accelerated approval pathway and obtain accelerated approval, and the potential for studies to be registrational or intended for registration; our development and regulatory strategy and approach for azenosertib, including our strategy to focus on bringing azenosertib to patients with PROC who are Cyclin E1+; our planned strategy, vision and path forward; the market opportunity for azenosertib, including the potential size of the patient population; existing data being supportive of the go-forward azenosertib development strategy the potential for azenosertib to be a very important treatment option; our plans to bring azenosertib to patients quickly and efficiently; the importance a Cyclin E1+ companion diagnostic for our go-forward strategy; the potential for the opportunity for azenosertib to be broad; our belief that a Cyclin E1+ companion diagnostic test substantially enhances the risk benefit profile of azenosertib; the encouraging nature of the azenosertib clinical data; the potential opportunities for azenosertib in combination or across different tumor types; our ability to recognize the benefits of our strategic restructuring; our belief that our resources are aligned and our strategy is highly focused; azenosertib’s therapeutic value as a single agent; the potential for Cyclin E1 to serve as a highly sensitive and specific predictive biomarker for response to azenosertib; the potential for azenosertib to be welcomed by the gynecological oncology community; the opportunity to improve outcomes in the next stage of development, including the potential for trial management and mitigation strategies to help in reducing the rate of discontinuations and improve duration on therapy and the potential for enhanced monitoring, guidance and supportive care to help increase the time on treatment; our positioning to execute; our projected cash runway; planned clinical trials for our product candidates; the potential of azenosertib to address a significant unmet need in patients with PROC who are Cyclin E1+; the potential benefits of azenosertib, including compared to available therapies and therapies in development (not head-to-head comparisons) and potential to improve patient quality of life; the potential unmet need in a particular indication and/or patient population; the timing and content of our anticipated milestones, including the timing of initiation of clinical trials and disclosure of clinical data; as well as statements that include the words such as “ahead,” “anticipate,” “believe,” “beyond,” “confident,” "continue," "could," “estimate,” “expect,” “forward,” “future,” “goal,” “go-forward,” “intended,” “may,” “milestone,” “ongoing,” “opportunity,” “path forward,” “plan,” “potential,” “predictive,” “promising,” “strategy,” "support," “vision,” “will” and similar statements of a future or forward-looking nature. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our plans, including the costs thereof, of development of a companion diagnostic; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; failure to identify additional product candidates and develop or commercialize marketable products; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; failure to obtain U.S. or international marketing approval; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; and significant costs as a result of operating as a public company. Other risks and uncertainties include those identified under the caption “Risk Factors” in our most recently filed periodic reports on Forms 10-K and 10-Q and subsequent filings with the U.S. Securities and Exchange Commission in the future could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management’s estimates as of the date of this presentation. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. While we may elect to update these forward-looking statements at some point in the future, we assume no obligation to update or revise any forward-looking statements except to the extent required by applicable law. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Neither we nor our affiliates, advisors or representatives makes any representation as to the accuracy or completeness of that data or undertake to update such data after the date of this presentation.​ Statements such as “not head-to-head,” “relative to historical data,” “relative to published data,” “direct cross-study comparison not intended” and similar references indicate that no head-to-head clinical trial has been conducted evaluating azenosertib against the indicated therapies. Notable differences exist between the Company’s trial designs, conditions under study and subject characteristics as compared to the evaluated third party results and caution should be exercised when comparing data across these studies.​ ZENTALIS® and its associated logos are trademarks of Zentalis and/or its affiliates. All other trademarks, trade names and service marks appearing in this presentation are the property of their respective owners. All website addresses given in this presentation are for information only and are not intended to be an active link or to incorporate any website information into this document.​ Zentalis’ product candidates are investigational drugs and have not yet been approved by the U.S. Food and Drug Administration or any other regulatory authority. Forward Looking Statements and Disclaimer

 
3 Opening Remarks Julie Eastland, Chief Executive Officer Azenosertib/WEE1 Biology and Cyclin E1 Overview Mark Lackner, PhD, Chief Scientific Officer 001 and MAMMOTH Results Ingmar Bruns, MD, Chief Medical Officer DENALI Part 1b Results Dave O’Malley, MD, The Ohio State University Comprehensive Cancer Center PROC Development Strategy Ingmar Bruns, MD, Chief Medical Officer Closing Remarks Julie Eastland, Chief Executive Officer Q&A Agenda for Today

 
4 Azenosertib Potential Best-in-Class Therapy for Cyclin E1+ PROC ➢ Recent launch of approved therapy in biomarker selected PROC demonstrates the large commercial opportunity ➢ Cyclin E1+ PROC, ~21,500 patients*, linked to poorer outcomes; no approved, targeted therapies ➢ SOC: mono chemo 4-13% ORR1 ➢ Other tumor types with Cyclin E1+ expression include breast, endometrial, bladder2 Market Opportunity ➢ >30% ORR and 5.5 mos mDOR in Cyclin E1+ patients at monotherapy dose of 400mg QD 5:2 ➢ 350+ PROC patients treated at active doses in monotherapy ➢ Manageable safety profile, potentially best-in-class WEE1 inhibitors Supportive Data ➢ Cash runway extended into late 2027 beyond anticipated topline data from DENALI Part 2 ➢ Resources now aligned with addition of key leadership on highly focused strategy ➢ Potential for accelerated approval pathway in PROC, Cyclin E1+ patients** Path Forward * US and EU4 (France, Germany, Italy, Spain) + UK; **Subject to supportive data and FDA feedback 1. Eskander, R., et al. Overcoming the Challenges in Drug Development, Front Oncol. 2023 Oct 17; 13:1258228 2. NAKAYAMA, K. et al. Int. J. Oncol. 48, 506–516 (2015); Aziz, D. et al. J. Pathol.: Clin. Res. 8, 355–370 (2022); Lotan, Y. et al. Eur Urol 64, 465– 471 (2013). Abbreviations: PROC, platinum-resistant ovarian cancer; mDOR, median duration of response; SOC, standard of care 3. Based on internal clinical data * PROC FRα+ ~35% Overlap <20% Cyclin E1+ ~50% 3

 
5 ORR^ mDOR SAFETY Solid Tumors ZN-c3-001 (Dose Escalation) Monotherapy, ≥300mg total daily dose, intermittent schedules 34.8%* (8/23) 5.2 mos Well tolerated across active doses and tumor types PARPi Resistant Ovarian Cancer MAMMOTH (ZN-c3-006) Monotherapy arm 400mg 5:2 31.3% (5/16) 4.2 mos Well tolerated in post-PARPi setting Similar TRAEs across doses Platinum Resistant Ovarian Cancer DENALI (ZN-c3-005) Monotherapy, 400mg 5:2 34.9% (15/43) 5.5 mos Safety profile consistent with 001 and MAMMOTH Similar Results Seen Across Studies in Cyclin E1+ PROC Therapeutic Doses Achieved with Manageable Safety Compared to Previously Developed WEE1 Inhibitors+ + Published data from other WEE1 inhibitors; Not a head-to-head comparison ^ Includes response evaluable patients who had received at least one post-treatment scan *PROC only Abbreviations: PROC, platinum-resistant ovarian cancer; mDOR, median duration of response; PARPi, poly (ADP-ribose) polymerase inhibitor; TRAE, treatment-related adverse event PROC, CYCLIN E1+ PATIENTS Data Cutoff Dec 2 2024 Active database; subject to further change

 
6 • Cyclin E1 overexpression increases CDK2 activity and accelerates G1-S transition, rendering cells more dependent on the DNA repair at the G2-M checkpoint • Inhibition of WEE1 activates CDKs, accelerates G1-S and G2-M transitions, and increases DNA damage to intolerable levels, resulting in mitotic catastrophe and cell death • CDKs and their cyclin binding partners promote progression through the cell cycle • Following DNA damage, WEE1 kinase inactivates Cyclin/CDK complexes at both G1-S and G2-M checkpoints to halt the cell cycle and allow for repair • Upon DNA repair, cells progress through the cell cycle and proliferate Cyclin E1 Overexpression Sensitizes Cancer Cells to Azenosertib Phosphorylation, causing inactivation of Cyclin1/2 DNA damageP G1 S G2 MDNA Damage Repaired CDK2 Inactive CDK2Cyclin E1 WEE1 P CDK1 Inactive WEE1 Cell Proliferation P Normal Cell Cycle Regulation Cancer Cell and Azenosertib Mitotic Catastrophe and Death G2-M Checkpoint DNA Damage Accumulates CDK2 Highly Active Driven by Cyclin E1 Overexpression Cyclin CDK Azenosertib WEE1 Azenosertib WEE1 CDK1 Active G1-S Checkpoint Cyclin E1 CDK2 G1 S G2 M Cyclin CDK G2-M Checkpoint G1-S Checkpoint

 
7 * Cyclin E1 IHC+ based on Zentalis proprietary IHC cutoff and Cyclin E1 IHC assay developed from the existing clinical data † Cyclin E1 IHC+% based on literature (~20% CCNE1 amplification) and the unbiased CCNE1 amp & Cyclin E1 overlapping data generated from Zentalis clinical trial samples ‡ Source: DRG Clarivate for US, UK and EU4 (France, Germany, Italy, Spain) IHC - immunohistochemistry • Cyclin E1+ is a biomarker of poor prognosis • Companion diagnostic ready for use in registration-intent studies Cyclin E1+ Tumors Comprise a Significant Portion of the PROC Population Including Vast Majority That Are CCNE1 Amplified ~20% of PROC The majority are also Cyclin E1+ All PROC ~50%† of PROC ~21,500‡ patients Cyclin E1 IHC+ * CCNE1 amplified Cyclin E1+ represents a significant opportunity in PROC

 
8 INDICATION TRIAL NAME + DEVELOPMENT APPROACH Solid Tumors ZN-c3-001 Dose-escalation monotherapy 274 Patients dosed 19 Study sites Fully enrolled PARPi Resistant Ovarian Cancer MAMMOTH (ZN-c3-006) Azenosertib monotherapy and in combination with niraparib 117 Patients dosed 22 Study sites Fully enrolled Platinum Resistant Ovarian Cancer DENALI (ZN-c3-005) Monotherapy at 400mg 5:2 102 Patients dosed 58 Study sites Part 1b - Fully enrolled Part 2 - Planned start 1H 2025 BRAF Mutant Colorectal Cancer ZN-c3-016 Azenosertib + encorafenib and cetuximab 44 Patients dosed 26 Study sites Escalation - Fully enrolled Azenosertib Initial Focus in Cyclin E1+ PROC

 
ZN-c3-001 Dose-Escalating Monotherapy Study in Solid Tumors NCT04158336

 
10 Total Enrollment First-in-Human Phase 1 Dose and Schedule Optimization in Solid Tumors: Therapeutic Window Established N=274 across all tumor types and dose* N=193 at total daily dose ≥ 300mg; evaluated for safety and anti-tumor activity ZN-c3-001 * Total enrollment (N=274) included cohorts for food effect (N=17) and relative bioavailability (N=38) Abbreviations: CRM, continual reassessment method; QD, once daily; BID, twice daily; 5:2, 5-days of treatment followed by 2-days off treatment; 4:3, 4-days of treatment followed by 3-days off treatment; DLT, dose limiting toxicity; PROC, platinum resistant ovarian cancer; USC, uterine serous carcinoma Intermittent Dosing Dose finding (CRM) Expansion (N=57)Dose Escalation (N=63) 450mg 500mg 400mg 400mg QD 5:2 350mg QD & 175mg BID 350mg QD 5:2 300mg QD 5:2 Total daily dose, 5:2 or 4:3 schedule Continuous Dosing Dose Escalation (N=59) Expansion (N=40) 450mg 200mg 400mg 350mg Lower doses (25-100mg) 300mg 300mg QD 200mg QD Total daily dose ≥ 300mg, including 175mg BID (N=193) Total daily dose < 300mg (N=26) Key Eligibility Status ✓ 1+ prior lines of therapy ✓ Solid tumor, PROC and USC enriched ✓ Tissue collected for biomarker analysis Fully Enrolled Optimal Dose Range

 
11 Heavily Pre-Treated Patient Population with Multiple Tumor Types; Patients with PROC had a Median of Five Prior Lines of Therapy PROC N = 69 USC N = 35 Other Solid Tumors* N = 89 Age (years) Median 66 66 64 Range (Min-Max) (48 – 83) (53 – 78) (26 – 81) ECOG PS (n, %) ECOG 0 19 (28%) 8 (23%) 32 (36%) ECOG 1 50 (72%) 26 (74%) 54 (61%) ECOG 2 0 1 (3%) 2 (2%) Prior Lines of Treatment Median (Range) 5 (1 - 19) 3 (0 - 12) 4 (0 - 11) 0 0 1 (3%)† 1 (3%)‡ 1-3 22 (32%) 22 (63%) 34 (36%) ≥4 47 (68%) 12 (34%) 54 (61%) *Anus, Appendix, Biliary tract, Bladder, Breast, Cecum, Cervix, Colon, Duodenum, Endometrium, Esophagus, Kidney, Lung, Other, Ovary, Pancreas, Peritoneum, Prostate, Rectum, Stomach, Uterus, Vulva/Vagina, including one patient who had unknown ECOG status; † patient had no prior therapy ; ‡ patient rolled over from the DDI study Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; SD, standard deviation; PARPi, poly-ADP ribose polymerase inhibitor; VEGFi, vascular endothelial growth factor inhibitor; PD-1/PD-L1, programmed cell death protein 1/programmed death ligand 1. Patient Demographics and Clinical Characteristics Total Daily Dose ≥ 300 mg – Continuous and Intermittent (N=193) PROC N = 69 USC N = 35 Other Solid Tumors N = 89 Prior Therapies (n, %) PARPi 46 (67%) 3 (9%) 5 (6%) VEGFi 60 (87%) 27 (77%) 39 (44%) PD-1/PD-L1 12 (17%) 27 (77%) 35 (39%) Cyclin E1 Status (n, %) Positive 26 (38%) 15 (43%) 9 (10%) Negative 29 (42%) 11 (31%) 25 (28%) Unknown 14 (20%) 9 (26%) 55 (62%) ZN-c3-001 Data Cutoff Dec 2 2024 Active database; subject to further change

 
12 Tolerable at Active Dose Levels Across Tumor Types Treatment Related AEs, n (%) Treatment-Related SAE 19 (9.8%) TRAE leading to dose reduction 76 (39.4%) TRAE leading to dose interruption 78 (40.4%) TRAE leading to discontinuation 10 (5.2%) TRAE leading to death 1 (0.5%) Treatment Related AEs*, n (%) All Grade Grade 3+ Gastrointestinal Decreased appetite 52 (26.9% ) 3 (1.6%) Diarrhea 100 (51.8%) 15 (7.8%) Nausea 117 (60.6%) 8 (4.1%) Vomiting 49 (25.4%) 2 (1.0%) Dehydration 22 (11.4%) 1 (0.5%) Fatigue 113 (58.5) 26 (13.5%) Hematologic Anemia 58 (30.1%) 22 (11.4%) Thrombocytopenia 51 (26.4%) 21 (10.9%) Neutropenia 29 (15.0%) 25 (13.0%) Febrile Neutropenia 2 (1.0%) 2 (1.0%) Safety Profile Total Daily Dose ≥ 300 mg – Continuous and Intermittent (N=193) • No gastrointestinal TRAE > G3 observed • Low rate of G3+ TR hematological toxicities, the majority G3 • Low rate of TRAE leading to treatment discontinuation • One G5 TRAE previously reported *TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules ZN-c3-001 Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: hematocrit decreased, hemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event. SAE, serious adverse event. Data Cutoff Dec 2 2024 Active database; subject to further change

 
13 Clinical Activity Overview - Total Daily Doses ≥ 300 mg - Continuous and Intermittent (N=193) Azenosertib Demonstrated Encouraging ORR and DOR at ≥300mg total daily dose, intermittent in PROC Tumor Type PROC USC Other Solid Tumors Dose Schedule Intermittent Continuous Intermittent Continuous Intermittent Continuous Cyclin E1 IHC Status All Cyclin E1+ All Cyclin E1+ All Cyclin E1+ All Cyclin E1+ All Cyclin E1+ All Cyclin E1+ Number of Patients 58 23 11 3 19 11 16 4 43 4 46 5 ORR, (%), n (95% CI) 20.7%, (12/58) (11.2 - 33.4) 34.8%, (8/23) (16.4 - 57.3) 18.8% (2/11) (2.3 - 51.8) 33.3% (1/3) (0.8 - 90.6) 26.3% (5/19) (9.2 - 51.2) 36.4% (4/11) (10.9 - 69.2) 18.8% (3/16) (4.1 - 45.7) 25.0% (1/4) (0.6 - 80.6) 2.3% (1/4) (0.1 - 12.3) 0.0% (0/4) (0.0 - 60.2) 4.3% (2/46) (0.5 - 14.8) 0.0% (0/5) (0.0 - 52.2) mDOR (mos) (95% CI) 5.1 (3.0, 5.9) 5.2 (2.8, 6.9) 7.1 (4.2, NE) 4.2 (NE, NE) 5.5 (5.4, NE) 5.5 (5.4, NE) 5.6 (4.1, NE) 6.9 (NE, NE) 4.3 (NE, NE) NA 3.3 (3.0, NE) NA ZN-c3-001 1 Not a head-to-head comparison PROC, platinum-resistant ovarian cancer; USC, uterine serous carcinoma; ORR, objective response rate; mDOR, median duration of response; IHC, immunohistochemistry; NE, not evaluable Greater anti-tumor activity seen with intermittent dosing schedule and Cyclin E1+ patients Results direct focused development on doses of 300 and 400 mg at intermittent dosing schedule Inter itt t All Cycli 58 20.7 , (12/58) (11.2 - 33.4) 34.8 , (8/23) (16.4 - 57.3) 5.1 (3.0, 5.9) 5.2 (2.8, 6.9) Data Cutoff Dec 2 2024 Active database; subject to further change

 
14 Key Takeaways from 001 Azenosertib studied in a large patient population across multiple tumor types Platinum-resistant ovarian cancer (PROC) identified as an indication particularly susceptible to WEE1 inhibition Cyclin E1 identified as predictive biomarker for response to azenosertib Meaningful therapeutic window identified providing a favorable risk-benefit profile in Cyclin E1+ PROC patients at total daily doses of 300 and 400mg QD 5:2 ZN-c3-001

 
MAMMOTH (ZN-c3-006) NCT05198804

 
16 MAMMOTH: Two Clinically-active Monotherapy Doses Studied in Heavily Pre-treated, PARPi-resistant PROC Patient Population Study Design ✓ 1-5 prior lines of therapy ✓ Platinum-resistant, progressed while receiving an approved PARP inhibitor ✓ Mandatory sufficient tissue for biomarker analysis Key Eligibility MAMMOTH Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate DOR, duration of response; PFS, progression-free survival; PROC, platinum-resistant ovarian cancer; PARPi, poly (ADP-ribose) polymerase inhibitor Azenosertib + niraparib Concurrent schedule (N=28) Azenosertib + niraparib Alternating schedule (N=28) Azenosertib monotherapy 300 or 400 mg QD 5:2 (N=61) TODAY’S FOCUS PFS Safety and Tolerability ORR, DOR Endpoints Enrollment (N=117) Enrollment CompleteStatus

 
17 Heavily Pre-Treated PARPi-resistant PROC Population 300 mg 5:2 (N=25) 400 mg 5:2 (N=36) Age (years) Median 71.0 63.0 Range (Min-Max) 45 – 80 31 - 84 ECOG PS (n, %) ECOG 0 7 (28%) 16 (44%) ECOG 1 18 (72%) 20 (56%) Prior Lines of Treatment (n, %) 1-3 15 (60%) 20 (56%) ≥4 10 (40%) 16 (44%) PARP 25 (100%) 36 (100%) Bevacizumab 24 (96%) 34 (94%) Cyclin E1 Status (n, %) Positive 13 (52%) 16 (44%) Negative 10 (40%) 15 (42%) Unknown 2 (8%) 5 (14%) MAMMOTH Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate DOR, duration of response; PFS, progression-free survival, PROC, platinum-resistant ovarian cancer Patient Demographics and Clinical Characteristics Monotherapy Cohorts Only Data Cutoff Dec 2 2024 Active database; subject to further change

 
18 Well-characterized Safety and Tolerability in PROC Monotherapy Cohorts at 300mg QD and 400mg QD (5:2) Doses Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: hematocrit decreased, hemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event. SAE, serious adverse event. 300mg (N=25) 400mg (N=36) Treatment-related AEs*, N (%) All Grade Grade 3+ All Grade Grade 3+ Gastrointestinal Decreased appetite 7 (28.0%) 1 (4.0%) 11 (30.6%) 0 Diarrhea 13 (52.0%) 0 17 (47.2%) 4 (11.1%) Nausea 15 (60.0%) 0 19 (52.8%) 1 (2.8%) Vomiting 2 (8.0%) 0 4 (11.1%) 1 (2.8%) Dehydration 0 0 0 0 Fatigue 6 (24.0%) 1 (4.0%) 11 (30.6%) 1 (2.8%) Sepsis 0 0 1 (2.8%) 1 (2.8%) Hematologic Anemia 10 (40.0%) 3 (12.0%) 14 (38.9%) 6 (16.7%) Thrombocytopenia 8 (32.0%) 2 (8.0%) 13 (36.1%) 4 (11.1%) Neutropenia 4 (12.0%) 3 (12.0%) 8 (22.2%) 5 (13.9%) Febrile Neutropenia 0 0 1 (2.8%) 1 (2.8%) Azenosertib Monotherapy 300 mg & 400mg QD (5:2) Treatment-related AEs, N (%) 300mg (N=25) 400mg (N=36) Treatment-Related SAE 4 (16.0%) 5 (13.9%) TRAE leading to dose reduction 11 (44.0%) 15 (41.7%) TRAE leading to dose interruption 11 (44.0%) 14 (38.9%) TRAE leading to discontinuation 4 (16.0%) 2 (5.6%) TRAE leading to death 0 (0.0%) 1 (2.8%) • Similar rates of TR SAEs across doses • Low rate of TR G3+ hematological toxicities with the majority being G3 events (only one G4 febrile neutropenia and one sepsis event) • Low rate of TRAEs leading to treatment discontinuation • One G5 TRAE previously reported * TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules MAMMOTH Data Cutoff Dec 2 2024 Active database; subject to further change

 
19 Azenosertib Monotherapy 300 mg & 400mg QD (5:2) Azenosertib Demonstrated Clinically Meaningful Responses in PARPi-resistant Monotherapy Cohorts Dose and Schedule 300mg 5:2 400mg 5:2 Cyclin E1 IHC Status All Cyclin E1+ All Cyclin E1+ Number of Patients 25 14 36 16 ORR, (%), n (95% CI) 20.0% (5/25) (6.8 - 40.7) 21.4% (3/14) (4.7 - 50.8) 22.2% (8/36) (10.1 - 39.2) 31.3% (5/16) (11.0 - 58.7) mDOR, months (95% CI) 4.9 (2.8 - NE*) 4.9 (3.0 - NE*) 5.5 (2.7 - NE*) 4.2 (3.0 - NE*) 400mg 5:2 shows numerically better ORR in Cyclin E1+ PROC patients compared to 300mg 5:2 *Not estimable due to small number of subjects and events Abbreviations: PARPi, poly (ADP-ribose) polymerase inhibitor; IHC, immunohistochemistry; QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate; CI, confidence interval; mDOR, median duration of response; NE, not evaluable MAMMOTH Data Cutoff Dec 2 2024 Active database; subject to further change

 
20 Key Takeaways from MAMMOTH Monotherapy Cohort Consistent antitumor activity in PARPi-resistant patients Tolerability and toxicity consistent with 001 study and similar between the assessed doses 400mg QD 5:2 showed numerically higher response rates than 300mg QD 5:2 MAMMOTH Learnings continue to support development of azenosertib in Cyclin E1+ PROC Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; PROC, platinum-resistant ovarian cancer; PARPi, poly (ADP-ribose) polymerase inhibitor

 
DENALI Part 1b (ZN-c3-005) NCT05198804

 
22 David M O'Malley, MD Director & Professor, Division of Gynecologic Oncology in Obstetrics and Gynecology John G. Boutselis Chair in Gynecologic Oncology The Ohio State University and the James Comprehensive Cancer Center

 
23 PARP Inhibitor or Bevacizumab + Olaparib Bevacizumab Combination Chemotherapy Platinum Doublet HRP PFI>6m PFI<6m PFI<6m Carboplatin + Paclitaxel High Unmet Need in Cyclin E1+ PROC Patients (2L+) Approved 2L+ Therapy Chemo Mono ORR 4 – 13%1 Mirvetuximab (FRα+ ~35% of PROC) ORR 32% - 42%2 No approved therapies specifically for Cyclin E1+ PROC Platinum Resistant Ovarian Cancer: High Unmet Need Provides Opportunity for Azenosertib Monotherapy First Line Maintenance Second Line Therapy First Line Therapy BRCAm/HRD Untreated Stage III/IV Ovarian Cancer PROC, platinum-resistant ovarian cancer; FRα, Folate Receptor alpha 1 Eskander, R., et al. Overcoming the Challenges in Drug Development, Front Oncol. 2023 Oct 17; 13:1258228;*2Clinical Trial SORAYA ORR 32%, MIRASOL ORR 42%

 
24 Standard of Care Single-Agent Chemotherapy has Low Efficacy in PROC New Options with Greater Efficacy Needed bev, bevacizumab; FRα, folate receptor alpha; mo, months; ORR, objective response rate; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; PROC, platinum-resistant ovarian cancer. 1. Pujade Lauraine E et al. Lancet Oncol. 2021;22(7):1034-1046, 2. Moore KN et al. ESMO 2019, 3. Gaillard SL et al. ESMO 2018, 4. Omatsu K ESMO 2020, 5. Pujade-Lauraine E et al. J Clin Oncol. 2014;32(13):1302–1308. Study Study Population Chemotherapy Arm ORR, % mPFS, mo mOS, mo JAVELIN Ovarian 2001 (n=190) ≤3 priors, 75% PROC and 25% Platinum refractory (28% prior bev) PLD 4 3.5 15.7 FORWARD I re-read2 (n=61) PROC 1–3 priors high FRα (33% prior bev) Paclitaxel or PLD or topotecan 6 3.2 12 CORAIL3 (n=199) PROC ≤3 priors (46% prior bev) PLD or topotecan 12 3.6 11 NINJA4 (n=159) PROC 77% >2 prior Gemcitabine or PLD 13 3.8 12.1 AURELIA5 (n=182) PROC ≤2 priors; 25% platinum refractory (8% prior bev) Paclitaxel or PLD or topotecan 13 3.4 13.3 Direct cross-study comparison of results from independently conducted clinical trials is not intended on this slide.

 
25 Study Design ✓ Platinum-resistant ovarian cancer ✓ 1-5 prior lines of therapy ✓ Tissue mandatory for biomarker assessment Key Eligibility DENALI Part 1b Evaluated 400mg 5:2 QD and Confirmed Cyclin E1 Biomarker DENALI Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate; DOR, duration of response; PFS, progression-free survival Endpoints PFS Safety and Tolerability ORR, DOR Enrollment (N=102) Azenosertib monotherapy 400 mg QD 5:2 Part 1b Enrollment CompleteStatus

 
26 DENALI Part 1b Evaluated 400mg 5:2 QD and Confirmed Cyclin E1 Biomarker Prior Therapies (n, %) Bevacizumab 93 (91%) PARPi 57 (56%) Cyclin E1 Status (n, %) Positive 48 (47%) Negative 46 (45%) Unknown 8 (8%) Age (years) Median 66 Range (Min-Max) 34 - 82 ECOG PS (n, %) ECOG 0 53 (52%) ECOG 1 49 (48%) Prior Lines of Treatment Median (Range) 3 (1-5) 1 8 (8%) 2 27 (27%) 3 32 (31%) 4 26 (26%) 5 9 (9%) DENALI Approximately Half of Patients Enrolled Were Cyclin E1 Positive Abbreviations: QD, once daily; 5:2, 5-days of treatment followed by 2-days off treatment; ORR, objective response rate; DOR, duration of response; PFS, progression-free survival; ECOG, Eastern Cooperative Oncology Group; PS, performance status Patient Demographics and Clinical Characteristics Data Cutoff Dec 2 2024 Active database; subject to further change

 
27 Consistent with Prior Studies, Safety and Tolerability Profile Remains Favorable Compared to Standard of Care Azenosertib 400mg QD 5:2 (N=102) Treatment Related AEs, N (%) Treatment Related SAE 22 (21.6%) TRAE leading to dose reduction 43 (42.2%) TRAE leading to dose interruption 60 (58.8%) TRAE leading to discontinuation 22 (21.6%) TRAE leading to death 2 (2.0%) Treatment Related AEs*, N (%) All Grade Grade 3+ Gastrointestinal Decreased appetite 23 (22.5%) 2 (2.0%) Diarrhea 51 (50.0%) 7 (6.9%) Nausea 67 (65.7%) 4 (3.9%) Vomiting 8 (7.8%) 2 (2.0%) Dehydration 11 (10.8%) 1 (1.0%) Hematologic Anemia 31 (30.4%) 11 (10.8%) Thrombocytopenia 35 (34.3%) 12 (11.8%) Neutropenia 16 (15.7%) 11 (10.8%) Febrile Neutropenia 3 (2.9%) 3 (2.9%) Pancytopenia 1 (1.0%) 1 (1.0%) Fatigue 61 (59.8%) 16 (15.7%) Sepsis 3 (2.9%) 3 (2.9%) • Safety profile consistent with 001 and MAMMOTH • Discontinuation rate higher than prior studies at the same dose – opportunity to improve in the future development • Two G5 TRAEs previously reported * TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules DENALI Comparison with SOC is not head-to-head Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: haematocrit decreased, haemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event; SAE, serious adverse event; LOT, lines of therapy. Data Cutoff Dec 2 2024 Active database; subject to further change

 
28 Cyclin E1+ Is a Strong Predictive Biomarker for Response to Azenosertib Abbreviations: IHC, immunohistochemistry; ORR, confirmed objective response rate; ITT, intent-to-treat † IHC+ based on proprietary IHC cutoff developed from Zentalis clinical data, non-Cyclin E1 IHC+ includes Cyclin E- (N=46) and Unknown (N=8) * Includes patients who received at least one post-treatment scan **Includes patients who received at least one dose of azenosertib 95% CI: 11.9 - 28.9 Overall Population Cyclin E1+ † Non-Cyclin E1 IHC+ † 34.9% (n=15/43) 6.0% (n=3/50) 31.3% (n=15/48) 5.6% (n=3/54) 95% CI: 21.0 - 50.9 95% CI: 1.3 - 16.6 19.4% (n=18/93) 17.6% (n=18/102) 10.8 - 26.5 18.7 - 46.3 1.2 - 15.4 Response Evaluable* ITT** Response Evaluable* ITT** Response Evaluable* ITT** DENALI O R R Data Cutoff Dec 2 2024 Active database; subject to further change

 
29 ORR ~35% in Response Evaluable Patients with Cyclin E1+ PROC - ORR in response evaluable* pts - 34.9% (15/43) (95% CI, 21.0-50.9) *Includes patients who received at least one post-treatment scan Abbreviations: CI, confidence interval; cPR, confirmed partial response; ORR, objective response rate; PD, progressive disease; SD, stable disease + + + + + + + = treatment ongoing # = best % change ~0% ‡ = received a post-baseline scan as SD but did not qualify as SD due to the post-baseline scan occurring outside of a protocol defined window-100 — -80 — -60 — -40 — -20 — 0 — 20 — 40 — 60 — 80 — 100 — B e st P e rc e n t C h an ge f ro m B as e lin e in S u m o f D ia m et e r (% ) PR PD PDSDcPRBest Overall Response DENALI # # # # ‡ ‡ Data Cutoff Dec 2 2024 Active database; subject to further change

 
30 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Treatment Duration (Months) B es t O ve ra ll R es p o n se mDOR ~5.5 months, Still Maturing at Data Cutoff Abbreviations: CI, confidence interval; cPR, confirmed partial response; mDOR, median duration of response; mPFS, median progression-free survival; PD, progressive disease; SD, stable disease; NE, not evaluable ‡ = received a post-baseline scan as SD but did not qualify as SD due to the post-baseline scan occurring outside of a protocol defined window - mDOR (mos) - 5.5 (95% CI, 2.7 - NE) - mPFS (mos) - 4.1 (95% CI, 2.8 - 6.8) α α β β α β γ α α α α ε α γ γ δ α DENALI Four ongoing responders as of December 2, 2024 Data Cutoff Off treatment for PD unless indicated otherwise: α Adverse event β Subject decision: all occurred soon after clinical hold γ Withdraw consent δ Investigator discretion ε Death PDSDcPRBest Overall Response Overall Response at Each Assessment PR NE ‡ ‡ Cyclin E1+ (N=48) Data Cutoff Dec 2 2024 Active database; subject to further change

 
31 Key Takeaways from DENALI DENALI DENALI Part 1b demonstrates azenosertib has the potential to provide greater benefit for patients with Cyclin E1+ PROC over available therapies* Cyclin E1 established as highly selective and predictive biomarker for response to azenosertib Favorable toxicity with opportunity to improve outcomes through mitigation strategies in the next stage of development Learnings lead us to the registration-intent trial, DENALI Part 2… *Not a head-to-head comparison

 
Integrated Data and Path to Registration in PROC

 
33 Azenosertib Monotherapy Studies Provide Large Amount of Safety Data and Meaningful Antitumor Activity to Support the PROC Registration-intent Study Well characterized safety profile in 356 patients Including PROC patients at 400mg 5:2 (N=165) and 300mg 5:2 (N=38) First-in-human in solid tumors dose escalation/expansion N=193 total daily dose ≥ 300mg PARPi resistant PROC 300mg & 400mg 5:2 N=61 PROC 400mg 5:2 N=102 001 MAMMOTH DENALI Part 1b Integrated efficacy analysis on Patients in PROC, Cyclin E1+ 400mg 5:2 (N=73) and 300mg 5:2 (N=20) Integrated Analysis

 
34 Safety and Tolerability at 300 and 400 mg 5:2 Broadly Comparable Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: hematocrit decreased, hemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event. SAE, serious adverse event. 300mg (N=38) 400mg (N=165) Treatment-related AEs*, N (%) All Grade Grade 3+ All Grade Grade 3+ Gastrointestinal Decreased appetite 8 (21.1%) 1 (2.6%) 40 (24.2%) 2 (1.2%) Diarrhea 18 (47.4%) 1 (2.6%) 86 (52.1%) 12 (7.3%) Nausea 23 (60.5%) 0 101 (61.2%) 6 (3.6%) Vomiting 3 (7.9%) 0 17 (10.3%) 3 (1.8%) Dehydration 1 (2.6%) 0 14 (8.5%) 1 (0.6%) Fatigue 14 (36.8%) 2 (5.3%) 90 (54.5%) 20 (12.1%) Sepsis 0 0 4 (2.4%) 4 (2.4%) Hematologic Anemia 13 (34.2%) 3 (7.9%) 53 (32.1%) 20 (12.1%) Thrombocytopenia 13 (34.2%) 2 (5.3%) 36 (21.8%) 8 (4.8%) Neutropenia 4 (10.5%) 3 (7.9%) 30 (18.2%) 21 (12.7%) Febrile Neutropenia 0 0 4 (2.4%) 4 (2.4%) Monotherapy Safety Profiles in PROC Patients 300 mg & 400mg QD 5:2 Treatment-related AEs, N (%) 300mg (N=38) 400mg (N=165) Treatment-Related SAE 6 (15.8%) 31 (18.8%) TRAE leading to dose reduction 13 (34.2%) 69 (41.8%) TRAE leading to dose interruption 16 (42.1%) 89 (53.9%) TRAE leading to discontinuation 5 (13.2%) 26 (15.8%) TRAE leading to death 0 3 (1.8%) * TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules • While numerically different, broadly comparable safety profiles at 300mg and 400mg 5:2 • Low frequency of previously reported G5 TRAEs, G3+ febrile neutropenia and sepsis observed at 400mg 5:2 Integrated Analysis Data Cutoff Dec 2 2024 Active database; subject to further change

 
35 Abbreviations: CI, confidence interval; cPR, confirmed partial response; mDOR, median duration of response; PD, progressive disease; SD, stable disease; NE, not estimable due to small number of subjects and events. 400mg 5:2 Shows Meaningful Response Rates >30% and mDOR >5 mos 300 mg 5:2 400 mg 5:2 ORR in response evaluable (95% CI) 22.2% (4/18) (6.4 - 47.6) 33.8% (23/68) (22.8 - 46.3) ORR in intent-to-treat (95% CI) 20.0% (4/20) (5.7 – 43.7) 31.5% (23/73) (21.1 – 43.4) mDOR (mos) (95% CI) 3.9 (2.8, NE) 5.5 (3.5, 6.3) + + + + + + + + + -100 — -80 — -60 — -40 — -20 — 0 — 20 — 40 — 60 — 80 — 100 — B es t P er ce n t C h an ge f ro m B as el in e in S u m o f D ia m e te r (% ) PR PD 300mg 5:2 (N=18) 400mg 5:2 (N=68) PDSDcPRBest Overall Response # # # # # # # # # ‡ ‡ ‡ + = treatment ongoing # = best % change ~0% ‡ = received a post-baseline scan as SD but did not qualify as SD due to the post-baseline scan occurring outside of a protocol defined window Integrated Analysis Data Cutoff Dec 2 2024 Active database; subject to further change

 
36 Clinically meaningful ORR > 30%, mDOR ~5.5 months Consistent efficacy across multiple monotherapy studies in heavily pre-treated patients Azenosertib Has Potential to be the First and Best-in-Class WEE1 Inhibitor in Cyclin E1+ PROC 1 Well characterized safety profile, favorable to SOC chemo1 Additional strategies implemented to further reduce risk and improve duration on therapy 2 Precise patient selection biomarker and convenient oral option provide unique advantage for azenosertib and may improve patient quality of life 3 1. Not a head-to-head comparison Abbreviations: ORR, overall response rate; mDOR, median duration of response; SOC, standard of care

 
37 Randomized Study vs. Standard of Care Same Patient Population Initiation Planned Post-Dose Confirmation Detail Design to be Discussed with FDA Abbreviations: 5:2 schedule = 5 days once-daily administration of azenosertib, followed by 2 days without azenosertib; IHC= immunohistochemistry; MIRV, mirvetuximab soravtansine; PROC=platinum resistant ovarian cancer. DENALI PART 2 FOR POTENTIAL ACCELERATED APPROVAL (N= ~100 at selected dose) PHASE 3 CONFIRMATORY STUDY (Pending FDA feedback) ✓ Platinum-resistant ovarian cancer ✓ 1-3 prior lines of therapy ✓ Prior MIRV if high FRα ✓ Cyclin E1+ by proprietary IHC cutoff criteria Key Eligibility Registration-Intent Studies for Azenosertib Monotherapy in PROC, Cyclin E1+ Population Part 2a (Alignment with FDA) Part 2b (Pending FDA feedback) Continuous Enrollment Across Part 2a and 2b with Dose Confirmation at Interim Analysis PROC Pts Cyclin E1+ Tumors 400mg 5:2 (N=30) 300mg 5:2 (N=30) 1:1 Randomization Dose TBD 5:2 (N=~70) Endpoints PFS Safety and Tolerability ORR, DOR P re sc re en in g / Ti ss u e C o n se n t Se am le ss E n ro llm en t Dose Confirmation

 
Closing

 
39 INDICATION TRIAL NAME + DEVELOPMENT APPROACH PHASE 1 PHASE 2 PHASE 3 MILESTONE* Studies for Lead Indication PROC Monotherapy DENALI Part 1b Updated Data at 1H 2025 Medical Meeting DENALI Part 2a + Part 2b Registration-intent Cyclin E1+ FDA Fast Track Designation Part 2a initiation 1H25 Topline Data 2026 Randomized Confirmatory Study Azenosertib vs. SOC chemo Cyclin E1+ Initiation 2026 Other Studies Ongoing Uterine Serous Carcinoma Monotherapy TETON (ZN-c3-004) FDA Fast Track Designation Data 1H26 Ovarian Cancer Combination ZN-c3-002 Azenosertib + multiple chemo backbones and bevacizumab Currently Enrolling BRAF Mutant Colorectal cancer Combination ZN-c3-016 Azenosertib + encorafenib and cetuximab Planned Data at 2025 Medical Meeting Ongoing Study Planned Study*Anticipated Extended Cash Runway Beyond Potential Registration Data Readout from DENALI Part 2 in Cyclin E1+ PROC Azenosertib Opportunity Remains Broad

 
40 Azenosertib Potential Best-in-Class Therapy for Cyclin E1+ PROC ➢ Recent launch of approved therapy in biomarker selected PROC demonstrates the large commercial opportunity ➢ Cyclin E1+ PROC, ~21,500 patients*, linked to poorer outcomes; no approved, targeted therapies ➢ SOC: mono chemo 4-13% ORR1 ➢ Other tumor types with Cyclin E1+ expression include breast, endometrial, bladder2 Market Opportunity ➢ >30% ORR and 5.5 mos mDOR in Cyclin E1+ patients at monotherapy dose of 400mg QD 5:2 ➢ 350+ PROC patients treated at active doses in monotherapy ➢ Manageable safety profile, potentially best-in-class WEE1 inhibitors Supportive Data ➢ Cash runway extended into late 2027 beyond anticipated topline data from DENALI Part 2 ➢ Resources now aligned with addition of key leadership on highly focused strategy ➢ Potential for accelerated approval pathway in PROC, Cyclin E1+ patients** Path Forward * US and EU4 (France, Germany, Italy, Spain) + UK; **Subject to supportive data and FDA feedback 1. Eskander, R., et al. Overcoming the Challenges in Drug Development, Front Oncol. 2023 Oct 17; 13:1258228 2. NAKAYAMA, K. et al. Int. J. Oncol. 48, 506–516 (2015); Aziz, D. et al. J. Pathol.: Clin. Res. 8, 355–370 (2022); Lotan, Y. et al. Eur Urol 64, 465– 471 (2013). Abbreviations: PROC, platinum-resistant ovarian cancer; mDOR, median duration of response; SOC, standard of care 3. Based on internal clinical data * PROC FRα+ ~35% Overlap <20% Cyclin E1+ ~50% 3

 
Q&A Julie Eastland Chief Executive Officer, President and Director Ingmar Bruns, MD Chief Medical Officer Mark Lackner, PhD Chief Scientific Officer David M O'Malley, MD Director & Professor, Division of Gynecologic Oncology in Obstetrics and Gynecology Liz Hickin VP, IR

 
ZN-c3-016 (BRAF+EGFR Combo in BRAF Mutant CRC)

 
43 ZN-c3-016: Phase 1/2 Trial in BRAF mCRC in Collaboration with Pfizer Data Cutoff Nov 25 2024 Active database; subject to further change Abbreviations: BRAF, V-Raf Murine Sarcoma Viral Oncogene Homolog B; mCRC, metastatic colorectal cancer; EGFR, epidermal growth factor receptor; MTD, maximum tolerated dose; RP2D, recommended phase 2 dose; ORR, objective response rate; PR, partial response; cPR: confirmed partial response; CR, complete response; DOR, duration of response; DCR, disease control rate; PFS, progression free survival; TR, treatment related; TTP, time to progression; 2L, second line • The most frequent treatment-related G3+ adverse events were asthenia (11.4%) and fatigue (6.8%) • DLTs were observed at the dose levels of azenosertib 300mg + encorafenib 150mg and azenosertib 400mg + encorafenib 75mg and included dose-limiting fatigue, atrial fibrillation, recurring elevated bilirubin (all Grade 3), and Grade 4 neutropenia • MTD was determined to be azenosertib 300mg + encorafenib 75mg • One TR G5 event previously disclosed: neutropenia, listeria sepsis • 12/34 (35%) BRAFi-naïve patients had confirmed response (2 CR, 10 PR) • 7/17 (41%) cPR in patients treated at azenosertib 300 mg + encorafenib 150 or 75 mg + cetuximab • No BRAFi-experienced patients (0/10) had confirmed response In the Dose Finding Phase 1, 44 patients were treated at various doses, including 10 BRAFi experienced patients: The results in BRAFi naïve patients are encouraging. However, with the evolving treatment landscape and resource prioritization, we decided not to advance into Phase 2 dose expansion portion of the study at this time ✓ BRAF V600E mutated mCRC ✓ Disease progression after 1 or 2 previous regimens for metastatic disease ✓ Prior therapy may include BRAF and/or EGFR directed therapy (e.g., may have progressed after BEACON regimen) Key Eligibility Primary Objectives Phase 1: Safety, tolerability, MTD, RP2D Phase 2: ORR, DOR, DCR, PFS, TTP Phase 1: Dose Finding Escalating dose levels of azenosertib + encorafenib + cetuximab Phase 2: Dose Expansion N=up to 82 patients NCT05743036 Encorafenib in combination with cetuximab (BEACON) is the standard of care for 2L treatment of BRAF V600E mCRC Safety Efficacy

 
Integrated Safety Analysis

 
45 Integrated Safety Analysis in All Patients Total Daily Dose ≥300mg (N=356) Neutropenia: Neutropenia, neutrophil count decreased, neutrophil percentage decreased; Thrombocytopenia: platelet count decreased and thrombocytopenia; Anemia: haematocrit decreased, haemoglobin decreased, RBC count decreased Abbreviations: AE, adverse event; TRAE, treatment related adverse event. SAE, serious adverse event. Monotherapy Safety Profiles in 001, MAMMOTH, DENALI Treatment Related AEs, N (%) TRAE leading to dose reduction 145 (40.7) TRAE leading to dose interruption 163 (45.8) TRAE leading to discontinuation 38 (10.7) TRAE leading to death 4 (1.1) Treatment related SAE 52 (14.6) Treatment Related AEs*, N (%) All Grade Grade 3+ Gastrointestinal Decreased appetite 93 (26.1) 6 (1.7) Diarrhea 181 (50.8) 26 (7.3) Nausea 218 (61.2) 13 (3.7) Vomiting 63 (17.7) 5 (1.4) Dehydration 33 (9.3) 2 (0.6) Hematologic Anemia 113 (31.7) 42 (11.8) Thrombocytopenia 108 (30.3) 39 (11.0) Neutropenia 57 (16.0) 44 (12.4) Febrile Neutropenia 6 (1.7) 6 (1.7) Pancytopenia 2 (0.6) 2 (0.6) Fatigue 191 (53.7) 44 (12.4) Sepsis 4 (1.1) 4 (1.1) • Well characterized, manageable safety profile in relatively large sample size • All Grade 5 TRAEs previously reported * TRAEs listed here represent adverse events of special interest and adverse events of clinical significance for azenosertib and this class of molecules Data Cutoff Dec 2 2024 Active database; subject to further change

 
v3.24.4
Cover
Jan. 29, 2025
Cover [Abstract]  
Document Type 8-K
Document Period End Date Jan. 29, 2025
Entity Registrant Name ZENTALIS PHARMACEUTICALS, INC.
Entity Incorporation, State or Country Code DE
Entity File Number 001-39263
Entity Tax Identification Number 82-3607803
Entity Address, Address Line One 10275 Science Center Drive
Entity Address, Address Line Two Suite 200
Entity Address, City or Town San Diego
Entity Address, State or Province CA
Entity Address, Postal Zip Code 92121
City Area Code (858)
Local Phone Number 263-4333
Written Communications false
Soliciting Material false
Pre-commencement Tender Offer false
Pre-commencement Issuer Tender Offer false
Title of 12(b) Security Common Stock, $0.001 par value per share
Trading Symbol ZNTL
Security Exchange Name NASDAQ
Entity Emerging Growth Company false
Entity Central Index Key 0001725160
Amendment Flag false
Entity Addresses [Line Items]  
Entity Address, Address Line One 10275 Science Center Drive
Entity Address, City or Town San Diego
City Area Code (858)
Local Phone Number 263-4333
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